Cyclization of the phosphate side chain of adenosine triphosphate: formation of monoadenosine 5'-trimetaphosphate.

Monoadenosine 5'-trimetaphosphate has been prepared from adeno-sine 5'-triphosphate by a carbodiimide-mediated condensation. The molecule was characterized by (3l)P nuclear magnetic resonance, and its (31)P spectrum was simulated through the assumption of a three-phosphorus spin system. The molecule is highly reactive and is rapidly converted to adenosine triphosphate upon contact with water.

2-aminoethylphosphonic Acid metabolism during embryonic development of the planorbid snail helisoma.

In freshly laid egg masses of Helisoma sp., more than 95 percent of the phosphorus is found in alkylphosphonic acids, as determined by phosphorus-31 nuclear magnetic resonance spectroscopy. These compounds are metabolized during embryonic development, as shown by differential acid hydrolysis and experiments with phosphorus-33-labeled phosphoric acid. Further, nuclear magnetic resonance spectroscopy indicates phosphonic acid involvement in related snail families, including the schistosomal vector Biomphalaria glabrata.

Biological phosphonates: determination by phosphorus-31 nuclear magnetic resonance.

Advanced methods of phosphorus-31 nuclear magnetic resonance spectroscopy provided a method whereby biological phosphonates and phosphates can be determined on simple lipid fractions of biological origin. The spectra consist of two easily distinguished resonance bands; one corresponds to families of phosphonates, and the other corresponds to families of orthophosphates.

Alkylphosphonates as unique compounds in the metabolism of the schistosomal vector Biomphalaria glabrata.

Examination of intact freshly laid egg masses of the schistosomal snail vector Biomphalaria glabrata by both 31P nuclear magnetic resonance spectroscopy and colorimetric phosphorus analysis indicated that 98% of the phosphorus in the egg masses was present in the form of alkylphosphonic acids. At least 87% of the total phosphorus originally present was comprised of 2-aminoethylphosphonic acid. During 11 days of embryonic development, alkylphosphonate-phosphorus decreased from 98% to 50% of the total phosphorus, indicating a possible role for phosphonate-phosphorus in the embryonic nutrition of these snails. Considering the relative uniqueness of the alkylphosphonates in nature, the very high concentration of these compounds in freshly laid eggs, and the reduction in their amount during embryonic development, the anabolic and catabolic pathways of alkylphosphonates may serve as sites for highly specific analogues in the control of these schistosomal vectors.

31P nuclear magnetic resonance-pH titrations of myo-inositol hexaphosphate.

With the use of 31P n.m.r. spectroscopy, the separate pKa values of each of the six phosphoric monoester groups of myo-inositol hexaphosphate were determined. The range of hydrogen-ion concentrations covered extended from that required for the phosphonium salts to that for the full dodecyl anion, and the determinations were carried out in the presence of sodium and tetrabutylammonium cations. The pKa for each phosphate grouping in the transition from the free acid forms of each group to the monoanion form of each group was determined to be: 1.1, C-2; 1.5, C-1 and C-3; 2.1, C-4 and C-6; and 1.7, C-5. In the mono- to di-anion transition, the pKa values were: 6.85, C-2; 7.60, C-5; 5.70 and 12.0, C-1 and C-3; and 10.0, C-4 and C-6. These data and the appearance of the 31P hexaphosphate n.m.r. multiplet are discussed in terms of conformations of myo-inositol hexaphosphate.

The comparison of individuals with recurrent tension-type headache and headache-free controls in physiological response, appraisal, and coping with stressors: a review of the literature.

It is widely accepted that stress plays an important role in the experience of tension-type headache. This article reviews the literature in which individuals with recurrent tension-type headache are compared to headache-free controls in the experience and appraisal of stress, psychophysiological response to stress, and coping with stress. A modified and extended version of the transactional model of stress as it might apply to tension-type headache is used to organize the relevant literature. In summary, there is evidence to suggest that individuals with recurrent tension-type headache experience more stressful events and are more sensitive and have a lower threshold to pain. There are some suggestions that headache sufferers may use different coping strategies for stress and pain. There is little evidence of differences in physiological responses to stressful events. The shortcomings of this body of literature are addressed and directions for future research are identified.

The menstrual cycle and migraine: a time-series analysis of 20 women migraineurs.

This study examined the prevalence of menstrually related headache and the relationship between the menstrual cycle and stress in a group of young women migraineurs sampled from a general population. Participants (N = 20) meeting International Headache Society criteria for migraine with or migraine without sure and not meeting criteria for menstrual migraine, provided daily headache activity, perceived stress, cognitive appraisal, and coping strategy data during two menstrual cycles. Multiple regression was used to analyze these data following a time-series approach in which the phases of the menstrual cycle were used as predictors of variation in each participant's headache, stress, appraisal, and coping data. Analyses revealed that fewer participants than expected showed significant relationships between their menstrual cycle and their headache activity (20%). However, for these women the amount of variation explained by the menstrual cycle was substantial. We suggest that, though some women's migraines vary with their menstrual cycle, the number of women substantially affected may be much smaller than has been estimated in the literature. Relationships between the menstrual cycle and the stress process were also found; however, inconsistencies between this and a previous study in our laboratory suggest that the nature of this relationship may vary across women migraineurs.

Migraine and stress: a daily examination of temporal relationships in women migraineurs.

This study examined daily temporal relationships between stress, cognitive appraisal, coping, and migraine in a group of young women migraineurs sampled from a general population. Participants (N = 20) meeting International Headache Society criteria for migraine with or migraine without aura provided headache activity, perceived stress, cognitive appraisal, and coping strategy data across 2 months of data collection. A time-series analytic approach was used to cross-correlate daily stress, appraisal, and coping data with daily headache data controlling for factors that can inflate correlations in data collected across time. Analyses revealed that between 50% and 70% of subjects showed significant, substantial, and meaningful temporal correlations between their daily stress and their daily migraine activity. Furthermore, these data support the hypothesis that stress and migraine are reciprocally related (ie, cyclically influencing each other across time). In addition, despite some measurement concerns, our data suggest that cognitive appraisal and coping are also related to migraine activity in a reciprocal fashion.

Appraisal of subjective stress in individuals with tension-type headache: the influence of baseline measures.

These studies investigated appraisal and coping strategies of tension-type headache sufferers and headache-free controls. In study 1, 60 women engaged in an interpersonal stressor. They completed measures that assessed subjective stress and coping strategies. Headache sufferers reported greater levels of stress at baseline than did controls but were not more reactive to a stressful interpersonal situation. All participants reported greater use of disengagement coping during the interpersonal interaction, while the amount of engagement coping strategies did not differ. Participants (30 women) in Study 2 engaged in progressive muscle relaxation. Headache participants again reported higher levels of subjective stress at baseline, this difference was nearly gone following relaxation. Together, the results suggest that individuals with tension-type headache report higher levels of subjective stress than headache-free controls when they make baseline ratings of stress and that this elevation cannot be attributed to the anticipation of a future stressful event.

Destructive bone disease in early syphilis.

Although destructive bone disease is a well-known complication of tertiary syphilis, osteitis or osteomyelitis are not commonly recognized as complications of early (primary or secondary) syphillis. A patient with secondary syphilis characterized by generalized lymphadenopathy, perianal condyloma lata, and positive rapid plasma reagin (RPR) and fluorescent treponemal antibody-absorption (FTA-ABS) tests also complained of headache, right should pain, and right anterior chest pain and swelling. Roentgenograms showed mottled osteolytic lesions consistent with previously described luetic bone disease. Biopsy confirmed the diagnosis of syphilitic osteomyelitis, and treatment with penicillin resulted in prompt resolution of symptoms.

Stress, headache, and physiological disregulation: a time-series analysis of stress in the laboratory.

This study examined the stress-headache relationship from a disregulation framework by monitoring both physiological responses (e.g., pulse, blood volume, skin resistance, and EMG) and self-reported responses to a stressful event in tension and migraine headache sufferers, as well as in headache-free controls. Responses were analyzed via time-series analyses to determine whether self-reports of stress were correlated with physiological measures of stress. It was hypothesized that tension and migraine headache sufferers would show fewer significant correlations than control participants between their self-reports of stress and physiological activity. Data analyses supported this hypothesis for tension headache sufferers, but generally not for migraine headache sufferers. The most compelling support for the hypothesis in tension headache sufferers came from the cross-correlations between self-reported stress and pulse rate.

Structural changes in myosin during contraction and the state of ATP in the intact frog muscle.

The reactivity of myosin to [14C]-labeled N-ethylmaleimide ([14C]NEM) or to tritium was determined in functionally different frog muscles. The incorporation of [14C]NEM into myosin decreased during isotonic or isometric contractions, as compared to resting muscle. The cysteine residues which were protected during contraction were not involved in the ATPase activity or the actin-binding ability of myosin. Peptide mapping revealed that several residues were protected simultaneously. The incorporation of tritium into the peptide N-H groups of myosin was also decreased during muscle activity. These data support the idea that activation and subsequent contraction of muscle are correlated with structural changes in the myosin molecule. The reactivity of myosin to [14C]NEM was increased when the muscle was stretched to 140% rest length and treated with iodoacetate to deplete ATP. Based on in vitro experiments and on literature data, it is suggested that in the resting muscle myosin contains bound MgATP which decreases the rate of incorporation of [14C]NEM into myosin and that upon the irreversible loss of ATP the rate increases. 31P nuclear magnetic resonance signals from a number of phosphates were detected in the intact frog muscle. The data indicated that the minimum concentration of ATP in the muscle is 3 mM, a value which agrees with that of chemical determination. The characteristic chemical shifts, coupling constants, and line widths of ATP in the muscle were considerably altered from that of either free ATP in aqueous solutions or ATP in perchloric acid extracts of muscle.

Cyclization of the phosphorus chain of the methylene-bridged analogs of adenosine triphosphate.

The phosphorus-containing side chains of two methylene-bridged analogs of adenosine triphosphate have been cyclized to produce the corresponding analogs of monoadenosine-5'-trimetaphosphate. (The structures are given in the journal.) The molecules, which were generated in anhydrous media through a carbodimide-mediated condensation, were characterized by 31P nuclear-magnetic resonance, and the white-noise 1H decoupled spectra were simulated. These molecules are quite reactive and readily converted to their corresponding linear forms upon hydrolysis. The second structure contains an asymmetric phosphorus atom, and both of the possible cyclic molecules have been observed and the diasteroisomeric mixture has been isolated.

Carbodiimide-intermediated esterification of the inorganic phosphates and the effect of tertiary amine base.

Detailed analysis of appropriate 31P nuclear-magnetic-resonance spectra shows that under the usual laboratory conditions, carbodiimide-induced condensation of orthophosphoric acid in a number of solvents leads to condensation only slightly beyond the metaphosphate composition in the presence of strong tertiary amines; whereas in the absence of amine, the condensation proceeds into the ultraphosphate region about halfway between the metaphosphate and phosphoric anhydride compositions. With amine, the principal product consists of the cyclic trimetaphosphate anion, with one of the nonbridging oxygen atoms substituted by the urea resulting from hydration of the carboiimide, i.e., (O2-) P-O-P(O2-) -O-P(O) [N[CH(CH3)2] see article [C(O)NHCH(CH3)2]] for the condensation with diisopropylcarbodiimide. Without amine, the major product is the 1,5-mu-oxotetrametaphosphate anion see article. The well-known carbodiimide-mediated phosphorylation of alcohols with orthophosphoric acid is shown to be directly attributable to the high reactivity of the phosphate branch groups of the carbodiimide-generated ultraphosphates.

Cardiac exposure history as a determinant of symptoms and emergency department utilization in noncardiac chest pain patients.

Although comparative studies differentiate noncardiac chest pain (NCCP), panic disorder, and coronary artery disease (CAD), little research has examined the defining features of NCCP, such as cardiac complaints, medical utilization, and learning history. We administered self-report measures to 80 Emergency Department (ED) patients with a primary complaint of chest pain who were subsequently found to not have CAD. Forty-eight percent of the ED utilization variance was accounted for by NCCP duration, age, cardiac distress symptoms, and prior exposure to both siblings' and friends' cardiac distress symptoms. In turn, 67% of the variance in cardiac distress symptoms was explained by education, age, NCCP duration, number of illnesses, noncardiac panic symptoms, prior exposure (friends), and prior observation of others' cardiac distress. No effects emerged for gender, ethnicity, avoidance, or depression. Results suggest that beyond the effects of age and distress intensity, prior exposure to other people's cardiac distress may influence NCCP.